Pyridines are important structural elements in a multitude of products in the chemical and pharmaceutical industry, and very many different processes for preparation are described in the literature. These can be divided roughly into processes in which the pyridine ring is built up, and those in which substituents are introduced (for example by electrophilic or nucleophilic substitution on the aromatic) or modified.
When 2-aminopyridine derivatives are required, they are usually prepared by introducing the amine substituent into a pyridine ring which is already present. Examples of such reactions are the Chichibabin reaction, i.e. the reaction of pyridines with sodium amide with elimination of sodium hydride, or the reaction of 2-halopyridines with nitrogen compounds (see, for example, Chem. Ber. 1936, 69, 2593 for the conversion of 3-amino-2-chloropyridine to 2,3-diaminopyridine).

However, these reactions have the disadvantage that either quite drastic conditions are needed (Chichibabin reaction, reaction of 2-halopyridines with aqueous ammonia), or that expensive noble metals and ligands are required for the conversion in the more recent catalytic variants (e.g. Org. Lett. 2001, 3, 3417).
A further disadvantage of the reactions described is the fact that the corresponding precursors must be available for the synthesis of pyridines with difficult substitution, which is often not the case. Moreover, for the introduction of the desired substituent into the desired position, an industrially performable process has to be available, which allows the conversion of the precursor beyond the laboratory scale.
This is often not the case especially when perfluoroalkyl groups (usually trifluoromethyl groups) are to be introduced into the pyridine ring. Some reactions here are described in the literature, such as the reaction of iodopyridines with (trifluoromethyl)trimethylsilane
or the conversion of methyl groups to trifluoromethyl groups by the action of chlorine and hydrofluoric acid.

However, all processes known to date have disadvantages which make use for the preparation of the aminopyridines sought unattractive, or rule it out. For instance, the aminopyridines are unstable under the drastic conditions of the conversion of methyl to trifluoromethyl groups. It would thus first be necessary to prepare other pyridine derivatives, for example halopyridines, and to perform the conversion of halogen to amine in a separate step, which results in complex and expensive processes. Owing to the high costs of the starting materials, the introduction of a trifluoromethyl group by conversion of an iodopyridine with the aid of (trifluoromethyl)trimethylsilane is likewise hardly attractive for the industrial scale.
It was accordingly an object of the present invention to provide a process with the aid of which the desired 2-aminopyridine derivatives can be prepared with high flexibility with regard to the substitution pattern and with which it is possible to prepare especially perfluoroalkyl-substituted, preferably trifluoromethyl-substituted, 2-aminopyridines.
A similar process has already been described for 2-halopyridines (WO2007/000249, whose United States equivalent is United States Patent Application Publication No. 2008/0214825 A1). In this process, a nitrile is first metallated and then reacted with a suitable carbonyl compound to give the hydroxynitrile. The final ring closure is then effected under strongly acidic conditions with HX (HCl, HBr, HI) or inorganic esters of these substances (e.g. SOCl2, POCl3, PCl5, PBr3 etc.) under very strongly acidic conditions. This reaction is illustrated by way of example for the synthesis of 4-trifluoromethyl-2-chloropyridine.

In order to be able to prepare the corresponding 2-aminopyridine proceeding therefrom, however, a further reaction with ammonia is needed, which proceeds only under severe conditions (see EP-B-0 228 846, whose United States equivalent is U.S. Pat. No. 4,762,928, or Dunn et al. in J. Fluor. Chem 1999, page 153) and requires high temperatures and high pressure.
